In their first rematch on Australian shores since losing to Keys for the Open title last year, the world No.1 found redemption with a 6-3 6-3 triumph at Pat Rafter Arena.
Sabalenka will meet Karolina Muchova in a semi-final to continue her Brisbane title defence, after the Czech talent knocked out third seed Elena Rybakina earlier on Friday.
The four-time grand slam winner had dominated Keys with her first serve and made just three unforced errors to take out the opening set.
A determined Keys recovered from match point on her serve, but Sabalenka wouldn't be denied and won in an hour and 29 minutes.
"She's a great player. Always tough battles against her," Sabalenka said.
"The whole match, I was trying to stay focused, stay in control, trying to put as much pressure on her serve.
"That's all I was trying to think about. I put so much pressure on her because yeah, she's aggressive."
Sabalenka has now claimed two straight-set victories over the world No.7 since losing last year's Australian Open final in three sets.
The 27-year-old steamrolled her American rival with a 6-0 6-1 semi-final win at Indian Wells last year.
Czechia's Muchova was the first woman to reach the final four after pulling off a 6-2 2-6 6-4 quarter-final win over Kazakhstan's world No.5.
The 2022 Wimbledon champion Rybakina lost her serve twice in a nightmare start against Muchova, making 16 unforced errors and three double faults in the opening set.
Muchova, who peaked at No.8 in the world in 2023 before undergoing wrist surgery the following year, set the tone early by forcing Rybakina to save two break points in the first game.
But the world No.20 was not without her fitness concerns, needing a medical timeout for restrapping her left ankle before the second set.
Gifted an eight-minute pause in play to recompose, third seed Rybakina broke to build a 3-1 lead before an unforced error from Muchova on her serve sent the match into a deciding set.
It was Muchova who came out on top to reach her first Brisbane International semi-final, defeating the 2024 champion on her serve after two hours and four minutes.
Aleksander Kovacevic claimed a 7-6 (7-3) 4-6 6-3 win over France's Giovanni in the first of the men's quarter-finals.
The American will face either Belgium's Raphael Collignon or compatriot Brandon Nakashima, who play later on Friday.
